A Center for Chemical Methodology and Library Design is proposed. The scientific focus of this Center will be the development of innovative combinatorial chemistry. The focus throughout is on techniques capable of leading to libraries containing molecules that (1) that utilize new principles of scaffold design (and especially the incorporation of multiple scaffold cores into a given library) and (2) are likely to have pharmacological activity based on sound drug design principles. This work will be facilitated through additional projects that focus on novel methods for phase trafficking and purification as well as organometallic chemistry. The proposed center will comprise three cores (administration, synthesis, and library design and analysis) and the following thematic scientific efforts: (1) New Phase-Trafficking Methodologies for Combinatorial Chemistry, (2) Biomimetics, (3) Organometallic Combinatorial Chemistry, and (4) Natural Products and Privileged Structures. Scientists at the University of Kansas, Kansas State University, and Iowa State University will direct the proposed work. It will be facilitated through the establishment of a centralized laboratory for combinatorial chemistry research in the newly acquired Life Sciences Research Laboratory (LSRL) at the University of Kansas in Lawrence, KS. The laboratory facility is adjacent to a high-throughput screening laboratory and other life science researchers in the Higuchi Biosciences Center, which will facilitate biological collaborations.